Life Sciences - Groups

Kassel-Schwiete Research Group: Development of Pharmacological Probes

Sebastian Thallmeier

Nowadays, computational modeling and theoretical methods are an important, indispensable aspect in life sciences aiming at more and more reliable modeling of more and more complex systems. Our group uses methods which work at different spatial and temporal resolution. For one thing, we apply quantum chemical methods which are based on the calculation of the wave function of the electron cloud around the classical nuclei. Secondly, we apply classical molecular dynamics with different resolutions. For the finer atomistic resolution, every atom is modeled as one particle. In contrast, atoms are grouped together in coarse-grained simulations. This simplifies the considered molecules and enables longer simulations of larger (bio)molecular systems. In general, more accurate methods require a larger computing effort. Thus, their application is limited to shorter processes and smaller systems.

The thematic focus of our group is in the fields of biophysics and medicinal chemistry. In particular, we are working on the development and characterization of pharmacological probes. Thereby, the investigation of the interactions between proteins and small molecules is crucial. Often, the small molecules interact only with one or a small group of proteins. Firstly, we aim at understanding why a molecule interacts strongly with certain proteins and not with others. Based thereon, we can alter the molecule in a defined way to strengthen the desired interaction. The goal is to develop molecules favorably interacting with specific proteins that play a role in diseases. The resulting pharmacologically active molecules can be experimentally synthesized, tested, and further improved. Thus, our research can contribute to the development of new medicines.

You can find further research topics, our scientific publications, as well as our engagement in public outreach on the pages Research and Publications. In the following, you can read the latest news from our group.

Fellow Detail

Research and Publications

News 2022

14.11.2022 — Last week, Cristina and Sebastian spent three days at the "2nd Martini Developers Meeting" on Malta. They had an intense exchange with the core development groups about current and future developments of the coarse-grained Martini force field.

03.11.2022 — Welcome Marieli Goncalves Dias! Marieli is a PhD student at the University of Campinas and the Brazilian National Biosciences Laboratory in Campinas, Brazil. She will spend one year in the Thallmair group to perform molecular dynamics simulations of nuclear receptors.

20.10.2022 — We developed an optimal description of cholesterol in the coarse-grained Martini force field. This prevents artificial temperature gradients in simulations of biological membranes. Together with colleagues at the CMMS and the MPI for Biophysics, we summarized our results in a preprint.

04.10.2022 — Our publication about photoswitchable cross-linkers was highlighted in an article in ChemistryViews entitled "Light-Responsive Linkers for the Control of Biomolecules".

08.09.2022 — The Tubby protein plays an important role for cellular communication. In collaboration with scientists from Marburg and Groningen, we were able to identify a previously unknown, second binding site for the signalling lipid PI(4,5)P2. It substantially increases the sensitivity of Tubby for the signalling lipid. You can find more details in this FIAS News article as well as in our Science Advances publication entitled "Two cooperative binding sites sensitize PI(4,5)P2 recognition by the tubby domain".

03.09.2022 — Photoswitchable cross-linkers are able to bind to biomolecules at two positions. Then, they can modulate the function of the biomolecules by means of light. Together with researchers of the University of Groningen, we developed and characterized such cross-linkers with improved water solubility. The results are now published entitled "Photoswitchable, water-soluble bis-azobenzene cross-linkers with enhanced properties for biological applications" in the journal ChemPhotoChem.

24.06.2022 — Our article on the frequency of crashes in molecular dynamics simulations entitled "Small ionic radii limit time step in Martini 3 molecular dynamics simulations" is now published in The Journal of Chemical Physics. In collaboration with researchers in CMMS and the MPI for Biophysics we developed solutions to enable larger time steps in Martini 3 simulations and thus to increase their efficiency. Thanks a lot for the nice collaboration, Balázs Fábián and Gerhard Hummer!

09.05.2022 — Last week, Cristina gave a talk entitled "Coarse-grained modeling of salbutamol and salmeterol binding to β2-adrenergic receptor" in the PhD student edition of the BioExcel webinar series. In case you missed Cristina's talk, have a look at the recording available at the BioExcel website.

13.04.2022 — Too large time steps in molecular dynamics simulations result in regular crashes of a simulation. We developed a statistical model for the frequency of these crashes together with colleagues at the CMMS and the MPI for Biophysics. The model as well as an analysis of crashes in simulations with the coarse-grained force field Martini 3 are summarized in our preprint.

11.04.2022 — Glutathione is responsible for the cellular redox potential and involved in cellular signaling pathways. In collaboration with researchers from Switzerland, we developed and characterized a quantitative sensor for glutathione. We show in our preprint that the sensor can be used in whole cells as well as in specific organells to determine the amount of glutathione.

01.04.2022Cristina was awarded a poster prize at the virtual school "BioExcel School on Biomolecular Simulations" for her poster "Coarse-grained modeling of salbutamol and salmeterol binding to β2-adrenergic receptor"! Now, she will present her research results in a talk during a BioExcel webinar on May 3rd. Congratulations, Cristina!

01.04.2022In collaboration with researchers of the University of Groningen, we wrote a perspective article about catalysis-induced motion of enzymes and its potential impact on cellular metabolism. You can read more about it in our publication entitled "Perspective: A stirring role for metabolism in cells" published in Molecular Systems Biology.

08.03.2022The development of light-switchable drugs is particularly challenging, because it combines elements of medicinal chemistry and photochemistry. Together with researchers from the Netherlands and Germany, we show in our publication in the Journal of Medicinal Chemistry how computational methods successfully contributed to design light-switchable inhibitors for a bacterial enzyme.

03.01.2022 — At high-light conditions, photosynthetic organisms have to protect themselves against too much light energy. In collaboration with scientists from the Netherlands and Italy we discovered that the protein structure and lipid affinity changes during a known regulatory mechanism. You can read more about the NMR experiments and coarse-grained MD simulations in our recent publication in Biophysical Journal.

01.01.2022 — The Thallmair Group wishes a Happy New Year!


Cristina Gil Herrero

Cristina Gil Herrero

PhD Student

Office: 0|301 (FIAS)
Phone: +49 69 798 47691

Marieli Goncalves Dias

PhD Student

Office: 0|300 (FIAS)
Phone: +49 69 798 47665

Former Members